Many ophthalmological conditions, such as diabetic retinopathy, age related macular degeneration, retinopathy of prematurity, arise from aberrant angiogenesis, driven in part by expression of vascular endothelial growth factor (VEGF) in response to the oxygen deprivation of cells. The oxygen tension within the retina of the eye is of primary concern in these diseases and is a function of supply (oxygen diffusion from the choroid and retinal capillaries) and demand (primarily from photoreceptors and nerve cells). The retina is a multilayered structure composed of various photoreceptor and nerve cells sandwiched between the retinal and choroidal blood supply. Consequently, oxygen delivery to the cells of the retina occurs by oxygen diffusion from either the retinal vasculature or the choroid. This puts an upper limit on the amount of oxygen that can be delivered to the cells within the retina. It has been shown that the metabolic demands of photoreceptors (primarily rods) are inversely proportional to the amount of light they are exposed to. Consequently, metabolic demands are significantly higher in the dark.
The increase in rod metabolism during dark adaptation can lead to hypoxia within the retina as demand outstrips diffusional supply. In patients with compromised retinal circulation, such as diabetics, the elderly, or premature babies, the effect is amplified. This is known as rod driven hypoxia and is becoming understood as a driver for pathogenesis.
Ultimately, treatment of ophthalmological pathologies with hypoxic etiology requires either reversing the oxygen deficiency or interrupting the resulting angiogenic cascade. Several approaches have been developed along these lines. The most clinically significant approach today is the administration of VEGF antagonists into the eye to block the signaling of angiogenesis. This can reduce the ingrowth of new blood vessels onto the retina which helps mitigate vision loss; however, it does not treat the underlying cause of the disease, hypoxia.
Other approaches have looked at enhancing oxygen delivery to the retina by means of implants, which locally increase oxygen tension around the retina to increase diffusional supply. Both passive devices, which shunt atmospheric oxygen from the surface of the eye through to the retina, and active devices, which generate oxygen through electrolysis, have been developed and demonstrated. The clinical efficacy of these approaches is currently awaiting further trials. Neither of these approaches however addresses the fact that dark adaptation drives hypoxia through increased rod metabolism.
It has been proposed that by stimulating the rod cells with low levels of light it may be possible to reduce their metabolic demand for oxygen and thereby reduce or eliminate hypoxia. PolyPhotonix Medical Ltd of Sedgefield, United Kingdom has produced a light emitting sleep mask, known as the Noctura, that utilizes this approach and has demonstrated clinically promising results. The approach however has a number of limitations. Firstly is compliance: sleep masks must be worn to be effective and even during clinical trials routine usage was not achieved. This arises from forgetfulness, inconvenience, and discomfort. Secondly is variability in dosage.